Effects of fiber content and its chemical treatment on the mechanical properties of screw pine fiber reinforced vinyl ester composite

Natural fiber-reinforced polymer composites have several advantages over traditional composites. The chemical modification of natural fibers helps to develop polymer composites with better mechanical properties. In the present work, mechanical properties such as tensile, flexural, and impact strength of chopped Screw pine fiber reinforced vinyl ester composites have been evaluated under-treated conditions based on the volume fractions of Screw pine fibers. The fibers have been treated with 5% of NaOH solution for 1 h at room temperature. The hand lay-up method has been used to prepare composite plates at room temperature. The results revealed that mechanical properties of composites increased with the increase of the fiber content up to 35.57 vol% at both the untreated and treated conditions and then dropped. However, the modulus values have been increased continuously from the fiber content of 8.43 to 45.3 vol%. It was identified that the critical or optimum fiber content for better mechanical properties is 35.57 vol% for both the untreated and treated conditions. The percentage of improvement at every combination was obtained by comparing the composites prepared with the untreated and treated fibers. The fractured surface of the treated fiber composites was examined by scanning electron microscopy. Moreover, the tensile properties are predicted using the Hirsch and Modified Bowyer and Bader model and compared with experimental values. The predicted results revealed that the Modified Bowyer and Bader model shows better conformity

In-vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide

This study reports on the release of a novel natriuretic peptide, CD-NP, from an in situ polymer precipitation delivery system. Following extensive screening of in-vitro release profiles, an in-vivo evaluation of the efficacy of the delivery system was carried out in Wistar rats. Gel injection was performed subcutaneously on the back of the rats. A secondary messenger, cyclic Guanosine 3′5′ Monophosphate (cGMP), was tested for verification of CD-NP bioactivity, in addition to direct measurements of CD-NP levels in plasma and urine using a radio-immuno assay. Plasma evaluation showed an elevated level of CD-NP over 3 weeks' duration. Unexpectedly, plasma cGMP level followed a decreasing trend over the same duration despite high CD-NP level. Loss of drug bioactivity was ruled out as a high level of CD-NP and cGMP excretion was observed in the treatment group as compared to baseline readings. This unexpected low-plasma cGMP levels and high-urinary cGMP excretion suggest that there might be other compensatory responses to regulation of the CDNP bioactivity as a result of the high drug dosing. The results stress the importance of assessing the overall bioactivity of released drug (in-vivo) concurrently in addition to measuring its concentrations, to determine the correct release profile.Published versio

Sustained delivery of a novel natriuretic peptide for three weeks with in situ polymer precipitation delivery system

CD-NP (Cenderitide) is a chimeric natriuretic peptide that acts on both the A and B natriuretic guanylyl cylcase receptors. This differentiated mechanism of action avoids the hypotensive nature of BNP while retaining the cardiac unloading and renal enhancing actions in heart failure (HF) together with direct anti-remodeling actions. CD-NP is being developed as an outpatient therapy for patients following hospital admission for HF, the “post-acute” period, to reduce rehospitalization. Our objective is to design an in situ polymer precipitation delivery system suitable for the chronic and sustained release of CD-NP. Methods 0.45% percentage weight/weight (w/w) CD-NP was mixed with 40% Poly (lactic-co-glycolic acid) in 39.55% w/w N-methyl-2-pyrrolidinone and 20% w/w triacetin. Resulting mixture was allowed to homogenize overnight. Three groups of 5 rats (Wistar Male, 250-300g) were injected subcutaneously with the gel. A fourth group (n=5) was injected with blank gels as vehicles. Rats sacrificed at respective time points (1/2/3 weeks) for plasma and urinary evaluation. Results Plasma CD-NP was significantly higher than vehicle 32,700 ± 2888 pg/ml, 13,977 ± 3302 pg/mol and 7,566 ± 1115 pg/mol at 1/2/3 weeks after gel injection. 24-hr urinary CD-NP excretion was significantly elevated at 107.3 ± 12.7 pg/min, 33.7 ± 29.7 pg/min and 16.5 ± 8.2 pg/min at 1/2/3 weeks as compared to 2.02 ± 0.10 pg/min pre-injection, while no significant difference was observed before and 3 weeks after gel injection in the vehicle group. Plasma cGMP was significantly elevated at 271.0 pmol/ml ± 41.4 at week 1 with a trend to be higher at weeks 2/3 as compared to vehicle. 24-hr urinary cGMP output was significantly elevated to 57.7 ± 2.9 pmol/min and 56.6 ± 7.4 pmol/min at week 1 and 2 as compared to pre-injection. Conclusion This study demonstrated that with the appropriate gel formulation, CD-NP release could be sustained over 3 weeks. The use of in situ polymer precipitation delivery system is a feasible and attractive technology for the delivery of the novel chimeric CD-NP in improving patient compliance and quality of life.Accepted versio

Cenderitide-eluting film for potential cardiac patch applications.

Cenderitide, also known as CD-NP, is a designer peptide developed by combining native mammalian c-type natriuretic peptide (CNP) and the C-terminus isolated from the dendroapis natriuretic peptide (DNP) of the venom from the green mamba. In early studies, intravenous and subcutaneous infusion of cenderitide was reported to reduce left ventricular (LV) mass and ameliorate cardiac remodelling. In this work, biodegradable polymeric films encapsulating CD-NP were developed and were investigated for their in vitro release and degradation characteristics. Subsequently, the bioactivity of released peptide and its effects on human cardiac fibroblast (HCF) were explored. We achieved sustained release from three films with low, intermediate and high release profiles for 30 days. Moreover, the bioactivity of released peptide was verified from the elevated production of cyclic guanosine monophospate (cGMP). The CD-NP released from films was able to inhibit the proliferation of hypertrophic HCF as well as suppress DNA synthesis in HCF. Furthermore, the sustained delivery from films showed comparable or superior suppressive actions on hypertrophic HCF compared to daily infusion of CD-NP. The results suggest that these films could be used to inhibit fibrosis and reduce cardiac remodelling via local delivery as cardiac patches

A fully degradable tracheal stent : in vitro and in vivo characterization of material degradation

We report on the testing of materials for a fully degradable tracheal stent. Such a stent has several advantages over currently used permanent stents made of metal or silicone polymers. However, the mode of degradation in the trachea is expected to be different from a fully submerged device, because of the uniqueness of the tracheal environment. A physical model was developed to allow an in-depth study of degradation of bioabsorbable polymers exposed to two differing media; namely 70 wt % water (gel) on one side and humidified air on the other, simulating conditions in a tracheal passage. Longitudinal microtome slices were obtained from both polymer surfaces and degradation kinetics data were derived from size exclusion chromatography. On the basis of the data obtained, it is observed that well-studied bulk-degrading polymers might show surface-eroding properties in such an environment. Generally, hydrophobic polymers retard the formation of a water concentration gradient and exhibit bulk-degradation kinetics. However, addition of specific plasticizers can influence the water uptake gradient, and force the polymer towards a pseudo “surface-eroding” behavior. In vivo studies in a rabbit model of degradable stents made from a selected polymer, demonstrate the feasibility of a fully bioabsorbable tracheal stent. This study aims to improve understanding of degradation of polymers under heterogeneous environments

24 hours Urinary cGMP Output.

<p>A) Treatment Groups B) Vehicle Group *P<0.05, Treatment vs Vehicle.</p

Blood Pressure Fluctuation over 18 days duration.

<p>A1) BP trend for CD-NP treatment groups A2) Magnified 3 days BP trend for treatment group B1) BP trend for vehicle group B2) Magnified 3 days BP trend for vehicle group. All timepoint is significantly different except for 0d and 12d, Compared between BP of treatment and vehicle group of the same timepoint.</p

Plasma Concentration Analysis

<p>. A) Plasma CD-NP concentration at 1/2/3 week timepoint B) Plasma cGMP concentration at 1/2/3 week timepoint *P<0.05, Treatment vs Vehicle.</p

The effect of polyethylene glycol structure on paclitaxel drug release and mechanical properties of PLGA thin films

Thin films of poly(lactic acid-co-glycolic acid) (PLGA) incorporating paclitaxel typically have slow release rates of paclitaxel of the order of 1 μg day−1 cm−2. For implementation as medical devices a range of zero order release rates (i.e. 1–15 μg day−1 cm−2) is desirable for different tissues and pathologies. Eight and 35 kDa molecular weight polyethylene glycol (PEG) was incorporated at 15%, 25% and 50% weight ratios into PLGA containing 10 wt.% paclitaxel. The mechanical properties were assessed for potential use as medical implants and the rates of release of paclitaxel were quantified as per cent release and the more clinically useful rate of release in μg day−1 cm−2. Paclitaxel quantitation was correlated with the release of PEG from PLGA, to further understand its role in paclitaxel/PLGA release modulation. PEG release was found to correlate with paclitaxel release and the level of crystallinity of the PEG in the PLGA film, as measured by Raman spectrometry. This supports the concept of using a phase separating, partitioning compound to increase the release rates of hydrophobic drugs such as paclitaxel from PLGA films, where paclitaxel is normally homogeneously distributed/dissolved. Two formulations are promising for medical device thin films, when optimized for tensile strength, elongation, and drug release. For slow rates of paclitaxel release an average of 3.8 μg day−1 cm−2 using 15% 35k PEG for >30 days was achieved, while a high rate of drug release of 12 μg day−1 cm−2 was maintained using 25% 8 kDa PEG for up to 12 days.NRF (Natl Research Foundation, S’pore)Accepted versio